Lipidomic analysis of lipid droplets from murine hepatocytes reveals distinct signatures for nutritional stress

Lipidomic analysis of lipid droplets from murine hepatocytes reveals distinct signatures for nutritional stress
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DOI:
10.1194/jlr.m028902
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发表时间:
2012-10-01
影响因子:
6.5
通讯作者:
Spener, Friedrich
Spener, Friedrich
中科院分区:
生物学2区
文献类型:
--
作者:
Chitraju, Chandramohan;Troetzmueller, Martin;Spener, Friedrich

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肝脏脂肪变性可由禁食或高脂饮食引起。我们通过脂质组学分析研究了这种代谢状态是否反映在正常饮食(FED)、禁食(FAS)或高脂饮食(HFD)小鼠肝细胞脂滴(LD)的脂质组中。LC-MS/MS在脂质种类谱和脂质分子种类水平上发现了富含三酰甘油(TG)分子种类的LD FAS表型(具有极长链(VLC)-PUFA残基)和HFD表型(除特征性脂质标志物种类外,不饱和TG种类较少)。营养应激并没有导致甘油二酯(DG)和磷脂(PL)类的显着结构变化。此外,散装TG和DG的分子种类表明伴随的从头TG合成和脂肪酶催化降解是活跃的LD。具有VLC-PUFA残基的DG种类将是磷脂酰胆碱(PC)种类的优选前体,其它为TG分子种类的优选前体。此外,PL类的分子种类适合肝细胞肯尼迪和磷脂酰乙醇胺甲基转移酶途径。我们证明了LD的脂质组学分析能够对营养应激进行表型分析。TG种类最适合这种表型,而TG,DG和PL分子种类的结构分析提供了代谢见解。奇特拉朱角,M.作者:J. Wolinski,G. G. Thallinger,A.拉斯河泽希纳河齐默尔曼,H. C. Kofeler和F.儿子来自鼠肝细胞的脂滴的脂质组学分析揭示了营养应激的不同特征。J. Lipid Res. 2012. 53:2141-2152。
Liver steatosis can be induced by fasting or high-fat diet. We investigated by lipidomic analysis whether such metabolic states are reflected in the lipidome of hepatocyte lipid droplets (LDs) from mice fed normal chow diet (FED), fasted (FAS), or fed a high-fat diet (HFD). LC-MS/MS at levels of lipid species profiles and of lipid molecular species uncovered a FAS phenotype of LD enriched in triacylglycerol (TG) molecular species with very long-chain (VLC)-PUFA residues and an HFD phenotype with less unsaturated TG species in addition to characteristic lipid marker species. Nutritional stress did not result in dramatic structural alterations in diacylglycerol (DG) and phospholipid (PL) classes. Moreover, molecular species of bulk TG and of DG indicated concomitant de novo TG synthesis and lipase-catalyzed degradation to be active in LDs. DG species with VLC-PUFA residues would be preferred precursors for phosphatidylcholine (PC) species, the others for TG molecular species. In addition, molecular species of PL classes fitted the hepatocyte Kennedy and phosphatidylethanolamine methyltransferase pathways. We demonstrate that lipidomic analysis of LDs enables phenotyping of nutritional stress. TG species are best suited for such phenotyping, whereas structural analysis of TG, DG, and PL molecular species provides metabolic insights.-Chitraju, C., M. Trotzmuller, J. Hartler, H. Wolinski, G. G. Thallinger, A. Lass, R. Zechner, R. Zimmerman, H. C. Kofeler, and F. Spener. Lipidomic analysis of lipid droplets from murine hepatocytes reveals distinct signatures for nutritional stress. J. Lipid Res. 2012. 53: 2141-2152.